Shedding the pounds as we enter our twilight years may be a harbinger of worsening brain health, suggests a new study published Monday in JAMA Neurology.

Analyzing the medical histories of 1,895 elderly but cognitively healthy people, the researchers found that those who reported greater amounts of weight loss from midlife to old age were more likely to later develop mild cognitive impairment (MCI) than those who hadn’t, even after accounting for other risk factors such as sex, education and the presence of known genetic markers for MCI and dementia. In particular, an average weight loss of 11 pounds per decade was associated with a 24 percent increased risk of developing MCI.

“These findings suggest that increasing weight loss per decade from midlife to late life is a marker for MCI and may help identify persons at increased risk for MCI,” the authors concluded.

The participants, aged 70 to 89 years, were earlier enrolled in the Mayo Clinic Study of Aging (MCSA), which first began in 2004. At the time of enrollment and every 15 months afterwards, participants were extensively examined for signs of worsening cognition and memory. MCI is often considered an early stage of dementia, with anywhere from 5 to 15 percent of MCI sufferers per year progressing to it, according to the authors. The past medical records of MCSA volunteers were also available to the researchers, allowing them to accurately trace their changing health and weight as they aged.

Over an average follow-up period of 4.4 years, 524 people developed MCI at an average age of 78.5, split almost equally between genders. While MCI sufferers were more likely to carry the APOE*E4 allele or be diagnosed with chronic conditions like heart disease and diabetes, the average weight lost between middle and old age was also greater in MCI sufferers than the still cognitively normal (4.4 pounds vs 2.6 pounds). This increased risk existed regardless of how much someone weighed in middle age; it was the weight loss itself that appeared to be linked to MCI. And after further analysis, weight loss was only associated with a subtype of MCI that came coupled with memory issues, suggesting a possible connection to the same mechanisms that cause Alzheimer's.

The study is only the latest to find a relationship between weight loss and dementia risk. While earlier research has specifically linked unintentional weight loss to dementia, the current authors said they weren’t able to definitively determine whether that was the case here. Given how consistent the association between weight change and MCI risk was in this study, though, we can likely chalk it up to unintentional weight loss, they said.

They note there are a number of theories as to why this link exists. For one, weight loss may simply be an early warning symptom of MCI/dementia, since it’s already known that a loss of appetite is often seen in the elderly, particularly the more frail they are. The phenomenon, likely the result of many complex factors, is so well established that researchers have taken to calling it the " anorexia of aging.” A person’s frailty may first lead to weight loss, then to MCI, and ultimately dementia. Psychological conditions like depression may also increase the risk of weight loss and MCI simultaneously. Likewise, it’s believed the same protein deposits that accumulate in the brain and can lead to dementia can also interfere with a person’s sense of smell, which in turn reduces calorie intake.

Regardless of which explanation fits best (or even if more than one does), the authors believe the “association of declining weight and BMI with MCI may have implications for preventative strategies for MCI.”

Source: Alhurani R, Vassilaki M, Aakre J, et al. Decline in Weight and Incident Mild Cognitive Impairment. JAMA Neurology. 2016.